Pulmonary fibrosis Flashcards
What is interstitial lung disease?
Wide range of diseases
At the most extreme end culminate in pulmonary fibrosis
7% of lung diseases culminate in ILD
Where does gas exchange take place in the lung?
Across fused basement membrane of the endothelial and epithelial cells
What is the space between the endothelial and epithelial basement membrane called?
Interstitial space
What is the histology of a normal intestitial space?
Narrow bridge of lung tissue
Populated by occasional fibroblast
What happens to the structure of the lung during ILD?
Increase in size of the interstitial space
Gas exchange is compromised
Fibroblastic foci around the alveolar capillary approach alveolar space
What does the lung look like in late stages of ILD?
Lung becomes scarred, fibrotic and difficult to see original structure
What is the lung’s response to injury?
Limited response
Hard to predict - depends on genetic background
Why is the lung easily injured?
Very exposed to toxins in the blood and allergens
What can be used to observe the response of lungs to injury?
CT scan
What are the 3 ways in which the lung can respond to injury?
Response can be:
Inflammatory - immune systen
Fibrotic scarring - fibroblast proliferation and ECM production
Or both
What is the role of T cells and macrophages in ILD?
Th2 produce IL 13 which works with TGF b to differentiate and proliferate the fibroblasts -> myofibroblasts
What induces the differentiation of fibroblasts -> myofibroblasts?
TGF b
IL 13
How do you diagnose pulmonary fibrosis?
Blood test and in-depth history to conclude source
Full history - jobs done and houses lived in
What are the 3 types of ILD?
Organising pneumonia
Interstitial pneumonia
Non-specific interstitial pneumonia
Characteristics of organising pneumonia
Whirls of not well organised fibroblasts
Not much ECM has been laid down
Patient will be left with some fibrosis
Characteristics of interstitial pneumonia
Most fibrotic form of lung response to injury
Whirls of fibroblasts produce ECM - highly proliferative
Honeycombing
Characteristics of non-specific interstitial pneumonia
Mixture of inflammatory cells
Airways pulled apart due to fibrosis
Underlying fibrosis when inflammation treated
What are the causes of pulmonary fibrosis?
Rheumatoid arthritis
Systemic sclerosis
Drugs and dust - asbestosis
Granulomatous disease
Idiopathic
What is Granulomatous disease?
Presense of granulomas in histopathology
Caused by
Sarcoidosis
Hypersensitivity pneumonitis - allergic response to inhaled exogenous substances
Characteristics of idiopathic pulmonary fibrosis
CT loss of lung capacity and interstitial shadowing at bases
Honeycombed appearance
Shortness of breath, clubbing, crackles, debilitating cough
Majority of patients die within 2 to 5 years after diagnosis
No cure - halt the decline via transplant
What are the 3 cells important in the development of pulmonary fibrosis?
Type I alveolar epithelial cells
Fibroblasrs
Neutrophils - unkown
How are Type I alveolar epithelial cells important in the development of pulmonary fibrosis?
Death and apoptosis of these cells during fibrosis
Replaces with type II epithelial cells
How are fibroblasts important in the development of pulmonary fibrosis?
Produce excessive amounts of EC collagen
Undergo proliferation
Resistant to apoptosis
What are common molecular targets in pulmonary fibrosis?
Fibroblasts -> myofibroblasts
Th2/ Th1 imbalance
MMP imbalance
Why is it difficult to develop drugs for ILD?
Initiating events are not known
Describe targetting fibroblast -> myofibroblast transition in developing drugs for ILD
Epithelial mesenchymal transition
Driven by TGFb
Activation of TGF b is dependent on integrin expressed
Can’t target TGF b - essential for other processes
Describe targetting Th1/Th2 imbalance
Inhibiting Th2 is beneficial to treating ILD
What is a biomarker for pulmonary fibrosis?
MMP
How do we taget MMPs to treat ILD?
Inhibition of MMPs is beneficial
Role of neutrophuls in development of pulmonary fibrosis
Patients with idiopathic pulmonary fibrosis = increased neutrophil count in bronchoalveolar lavage
The more neutrophils = the worse the outcome
Pathogenesis of pulmonary fibrosis
Epithelial cells undergo inkury
Chemokines are released from local cells and macrophages
This recruits neutropjils
Form ROS - more damage to cells
More TGF b produced
More EMT transition and epithelial cells transform into myofibroblasts
Increased deposition of ECM
